Correction to: Recommendations for follow­up of colorectal cancer survivors.

In the published article, the following information was missing.

Recommendations for follow-up of colorectal cancer survivors.

Colorectal cancer (CRC) is one of the tumours with the highest incidence and mortality in the Spanish population. Nevertheless, the advances in prevention and treatment have contributed to an increased number of patients who survive for prolonged periods of time. In addition, despite recurrences, improved survival following metastasis resection is likewise on the rise. This underscores the importance of carrying out follow-up programmes even in low-risk patients for the early detection of recurrence. The main objective of this article is to provide a set of recommendations for optimising the follow-up of CRC survivors as well as for managing the sequelae that result from either pharmacological or surgical treatment.

Pro- and anti-inflammatory cytokine gene single-nucleotide polymorphisms in inflammatory bowel disease.

Anti-inflammatory cytokines have an important role in disease, tumour and transplant processes. Alterations in the regulation of several cytokines have been implicated in a variety of inflammatory disorders, including IBD (inflammatory bowel disease) [Crohn's disease (CD) and ulcerative colitis (UC)]. Cytokine polymorphisms are also known to affect the level of gene expression. Thus, the aim of this study was to determine the relationship between cytokine polymorphisms and the IBD pathologies in a Spanish population. Polymorphisms analysis was performed using PCR-SSOP using a microbeads luminex assay. The following polymorphisms were determined: TNFα [-238G/A (rs361525) and -308G/A (rs1800629)], IFNγ [+874A/T (rs62559044)], TGFß [+869C/T (rs1982073) and +915G/C (rs1800471)], IL10 [-1082A/A (rs1800896), -592A/C (rs1800872), -819C/T (rs1800871)], IL6 [-174C/G (rs1800795)], IL12p40 [3'UTR -1188A/C (rs3212227)], IL1α [-889C/T (rs1800587)], IL1ß [-511C/T (rs1143634) and +3962C/T (rs1143633)], IL1R [Pst-1 1970C/T] and IL1RA [Mspa-1 11100C/T]. No statistical differences in TNFα, IFNγ, TGFß, IL10, IL6, IL1α, IL1ß, IL1R and IL1Ra genotypes and allele distributions between the IBD groups and healthy controls were found. However, we observed significant differences in the 3'UTR -1188A/C polymorphism of IL12p40. So -1188A allele was increased in patients with UC and the -1188C allele (high IL12p40 production) was increased in patients with CD with respect to controls. These data are in concordance with the fact that CD has been shown to be associated with a Th1 T-cell-mediated inflammation model and high IL12/IFNγ production at histological affected sites. These data suggest that cytokine polymorphisms in TNFα, IFNγ, TGFß, IL10, IL6 and IL1α, IL1ß, IL1R and IL1Ra cytokine gene do not seem to be relevant in IBD susceptibility and IL12p40 3'UTR -1188A/C polymorphism seems to be associated with a differential IBD development.

Effect of oral anticoagulants on the outcome of faecal immunochemical test.

BACKGROUND: We aimed to evaluate whether oral anticoagulants (OACs) alter faecal immunochemical test (FIT) performance in average-risk colorectal cancer (CRC) screening. METHODS: Individuals aged 50-69 years were invited to receive one FIT sample (cutoff 75 ng ml(-1)) between November 2008 and June 2011. RESULTS: Faecal immunochemical test was positive in 9.3% (21 out of 224) of users of OAC and 6.2% (365 out of 5821) of non-users (P-trend=0.07). The positive predictive value (PPV) for advanced neoplasia (AN) in non-users was 50.4% vs 47.6% in users (odds ratio, 0.70; 95% CI, 0.3-1.8; P=0.5). The PPV for AN in OAC more antiplatelets (aspirin or clopidogrel) was 75% (odds ratio, 2; 95% CI, 0.4-10.8; P=0.4). CONCLUSIONS: Oral anticoagulant did not significantly modify the PPV for AN in this population-based colorectal screening program. The detection rate of advanced adenoma was higher in the combination OAC more antiplatelets.

Genetic polymorphisms of tumour necrosis factor alpha (TNF-α) promoter gene and response to TNF-α inhibitors in Spanish patients with inflammatory bowel disease.

Tumour necrosis factor alpha (TNF-α) has an important role in inflammatory response. Alterations in the regulation of TNF-α have been implicated in a variety of inflammatory disorders, including Inflammatory bowel disease (IBD). Indeed, a common treatment for IBD is the use of TNF-α inhibitors. Polymorphisms in the TNF-α promoter region are known to affect the level of gene expression. Our aim was to investigate the influence of these single nucleotide polymorphisms (SNPs) in TNF-α promoter gene play in the risk of IBD in a Spanish population and their individual response to anti-TNF-α treatment. DNA samples from patients with IBD and controls were screened for TNF-α -238G/A (rs361525) and -308G/A (rs1800629) SNPs by PCR-SSOP using a microbeads luminex assay and compared with response to TNF-α inhibitors. There were not statistical differences in -238G/A and -308G/A allele and genotype frequencies between patients. However, we found an increased frequency of -308A allele and -308GA genotype in these nonresponders patients to TNF-α inhibitors with respect to responders patients (Pc < 0.05). This -308GA genotype has been classified as high producer of this cytokine. This fact could actually be interesting to explain the different response of patients with IBD with respect to TNF-α inhibitors. TNF-α promoter gene polymorphism does not seem to play a role in IBD susceptibility, but particular TNF-α genotypes may be involved in the different responses to TNF-α inhibitor treatment in Spanish patients with IBD.

Prevention or cure in times of crisis: the case of screening for colorectal cancer.

Colorectal cancer is a serious health problem in which screening is capable of reducing both the mortality and the incidence of the disorder. Colonoscopy, the mainstay of this type of screening, allows to establish an early diagnosis and also to eliminate malignant precursor lesions. The screening test which is performed in Spanish programs is the determination of fecal occult blood using the immunochemical method which gives around 70% of positive values for colonoscopy for any type of neoplasia. As a result, in 2009 the National Health System set as an objective that these programs cover 50% of the population by 2015. It is well known that colon screening is highly cost effective with a ratio of around 2500€ per QALY, much lower than ratios of other programs. Only the direct costs of colon and rectal cancer in Spain can be estimated at more than one thousand million euros per year. Early diagnosis and the cancers avoided thanks to screening can reduce these costs by 40%. The impact that the introduction of this screening has on health services can be lessened if the indications for colonoscopy are followed adequately. In conclusion, there is no justification for not acting to prevent CRC and this is especially so in times of crisis as there is no better social cost invested than that which saves suffering, deathsand even money.

Double-balloon enteroscopy in two dogs.

It is difficult to insert a flexible endoscope deep into the small intestine. A new method, double-balloon enteroscopy, has been developed to improve access to the small intestine, and the aim of this study was to evaluate its usefulness for examination of the small intestine of dogs. The method uses two balloons, one attached to the tip of the endoscope and another attached to the tip of an overtube. The double-balloon endoscope is advanced through the intestine by being held alternately by the balloon on the endoscope and the balloon on the overtube. The technique was applied in two dogs of medium size, using both oral and anal approaches, and it was possible to examine the whole surface of the mucosa of their small intestines.

Clinical evolution in the first 3 months of patients after liver transplantation in maintenance phase converted from mycophenolate mofetil to mycophenolate sodium due to gastrointestinal complications.

The enteric-coated mycophenolate sodium (EC-MPS) is a new formulation of mycophenolic acid with a gastro-resistant enteric coating, which releases the drug in the intestine, reducing the incidence of the gastrointestinal (GI) adverse effects. The present work provided a summary of 20 patients with liver transplantation and more than a 1 year of treatment with mycophenolate mofetil (MMF) who, after presentation of GI complications, were converted to EC-MPS. The patients were followed over a 3-month period after beginning EC-MPS treatment. The mean age of the cohort was 53 +/- 10 years and included 75% men. The reasons for transplantation were ethanol cirrhosis (70%), hepatitis C cirrhosis (30%), hepatocarcinoma (5%), and Wilson's disease (5%). At baseline, all patients were being treated with cyclosporine (CsA). CsA doses and levels were reduced during follow-up: baseline dose 179 mg/day versus 143 mg/day at 3 months; levels: 90.4 ng/mL versus 85.8 ng/mL, respectively (P = .017). The administered dose of EC-MPS was 720 mg/day in all cases. The GI complications at baseline were: diarrhea 60% (92% moderate-severe), abdominal discomfort 60% (58% moderate), abdominal pain 45% (44% moderate-severe), gas 40% (38% moderate-severe), nausea 20% (25% moderate), and dyspepsia 20% (mild). After 3 months of EC-MPS treatment, only two patients (10%) displayed moderate diarrhea. The renal evolution was favorable, serum creatinine was reduced, and 24-hour creatinine clearance significantly increased (creatinine: 1.78 +/- 1.6 mg/dL at baseline versus 1.30 +/- 0.3 mg/dL at 3 months, P = .002; creatinine clearance: 72.8 +/- 18 mL/min versus 79.6 +/- 13 mL/min, P = .001). Conversion of MMF to EC-MPS in liver transplant recipients solved the GI tolerability problems and improved renal function during the first 3 months, probably due to the concomitant reduction of anticalcineurinic dose.

[Gastrointestinal bleeding caused by small bowel leiomyosarcoma]. / Hemorragia digestiva por leiomiosarcoma de intestino delgado.

The small bowel leiomyosarcoma is a infrequent tumour in the clinical practice. We report the case of a 50 year old male admitted to the hospital on two occasions for gastrointestinal bleeding. On the second occasion a push enteroscopy located in jejunum a tumour. The pathologic diagnosis was a low grade jejunal leiomyosarcoma. The patient required a surgical intervention with resection of the affected portion of the jejunum.

Double-balloon enteroscopy: a descriptive study of 50 explorations.

AIM: To evaluate the utility of double-balloon enteroscopy for small-bowel disease. DESIGN: A prospective study of 50 consecutive enteroscopies performed from December 2004 to July 2005 to analyze diagnoses and treatments. PATIENTS: 44 patients (33 had undergone a previous capsule endoscopy) with indications for obscure digestive hemorrhage, angiodysplasia, Peutz-Jeghers syndrome, ulcer, suspected Crohn's disease, tumors, and refractory celiac disease. RESULTS: We carried out enteroscopy studies in 44 patients by the oral route and, in 6 additional patients, by both the oral and anal routes. We reached the ileon with the oral route in all cases but one (jejunal stenosis), and in 4 cases out of 7 with the anal route, with an average duration of 73 minutes. We found angiodysplasia in 19 cases, as well as NSAID-related enteropathy, Crohn's disease, diverticulosis, and Waldenström's disease. We performed biopsies in 31% of cases with diagnoses of adenocarcinoma, lymphangiectasia secondary to tumor in celiac disease, and Whipple's disease. We treated 19 patients with angiodysplasia (1 to 20 synchronous lesions) with argon, and 4 patients with polyps using polipectomy (sporadic polyps or Peutz-Jeghers syndrome). A retained capsule in one patient with stenosis was removed. CONCLUSIONS: Double-balloon enteroscopy is a useful and effective technique in the diagnosis and treatment of small intestine diseases, thus complementing capsule endoscopy. More studies are needed to analyze its impact on the management of this condition.

[Review of ethical aspects in biomedical research. The experience of the Ethics Committee of the Center for Toxic Oil Syndrome and Rare Diseases [CISATER]]. / Revisión de los aspectos éticos en la investigación biomédica: la experiencia del Comité de Etica del Centro de Investigación sobre el Síndrome del Aceite Tóxico y Enfermedades Raras (CISATER).

This Field Note aims to make known the decisions taken by the Ethics Committee of the Instituto de Salud Carlos III for Toxic Oil Syndrome regarding the secondary use of research specimens in biological research when informed consent is lacking. This is a common concern in the field of biomedical research. After debating the ethical suitability of the secondary use of these samples, our main conclusion is that researchers conducting prospective studies should expressly solicit written informed consent from participants in the study about i) whether there will or could be any secondary use of the samples and, if so, ii) whether such secondary use would be conditional on the type of research.

Prevalence and associated factors for gallstone disease: results of a population survey in Spain.

We conducted a cross-sectional survey to determine the prevalence of gallstone disease (gallstone or cholecystectomy) in a random sample of the adult population of Guadalajara, Spain. The sample stratified by age and sex was drawn from the municipal census. Stratum sample sizes were proportional to population sizes and to the expected prevalence rates calculated through a meta-analysis of the European literature. The screening protocol included a gallbladder ultrasonography, a questionnaire on personal and family history, a physical examination, and a blood sample for biochemical determinations. The response rate was 61.2%. The overall prevalence of gallstone disease was 9.7% (95% CI, 7.3-12.0). Prevalence was higher (but not statistically significant) in women (11.5%; 95% CI, 8.2-14.7) than in men (7.8%; 95% CI, 4.6-11.1). After controlling for confounding by multiple logistic regression, increasing age, body mass index, dyspeptic symptoms, smoking habit, and use of hypolipidemic drugs were positively associated with gallstone disease. Total serum cholesterol and alcohol consumption were negatively associated.

Clinical value of an automated granulocyte elastase assay in predicting severity of acute pancreatitis.

OBJECTIVE: Quantification of circulating levels of granulocyte elastase has been shown to be a reliable method to predict severity of acute pancreatitis. The ELISA method until now available is, however, not easily applicable to the clinical routine. MATERIAL AND METHODS: In the present study we analyzed, retrospectively the clinical usefulness of an automated granulocyte elastase assay, the immunoactivation (IMAC) procedure, in predicting the course of acute pancreatitis, and we compared it with the ELISA method. PATIENTS: Plasma samples from 39 patients with acute pancreatitis, 18 with mild episodes and 21 with severe disease, were analyzed for granulocyte elastase concentration by both automated and manual ELISA procedures, on admission and on days 1, 2, 3, 5, 7 and 10. RESULTS: Automated elastase values did not differ statistically (Mann-Whitney test) from manual granuloma elastase values obtained by ELISA. Higher plasma elastase concentration was invariably found in severe pancreatitis when compared to mild cases. The optimal discriminating (severe vs mild illness) cutoff values were 200 micrograms/L on admission and 250 micrograms/L at 24 hours. Both assays showed similar prognostic reliability upper 90 per cent. CONCLUSIONS: Automated procedures enable faster and simpler granulocyte elastase determinations and exploit the benefits of this early and efficient prognostic marker.

Inflammatory response in the initial phase of acute pancreatitis: relationship to the onset and severity of the disease.

Pathophysiological theories on acute pancreatitis and its complications have been always based on the harmful role played by the activated pancreatic digestive enzymes at local and systemic levels. However, acute pancreatitis is an inflammatory disease in which a complex systemic response is produced, which involves the interaction of cells (neutrophils, monocytes/macrophages, platelets, lymphocytes, endothelial cells and fibroblasts) and different proteolytic systems (coagulation, fibrinolysis, kallikrein and complement systems). The more or less severe evolution of the disease may depend on the intensity of this inflammatory response, according to the potential capacity of its mediators to cause significant damage at local and systemic levels. The initial mechanism of this response may be the release of oxygen free radicals by the damaged pancreatic cells, which are able to activate the cascade of digestive pancreatic enzymes and initiate chemotaxis and activation of inflammatory cells. Based on the actual knowledges, the present article aims to analyze the role of the inflammatory response on the severity of acute pancreatitis.

[Colorectal cancer: its incidence in the province of Guadalajara]. / Cáncer colorrectal: su incidencia en la provincia de Guadalajara.

The present study was designed to establish the incidence of colorectal cancer in the province of Guadalajara. During an 8-year-period, 347 cases of colorectal cancer were detected. The adjusted global incidence rate of colorectal cancer was 15.4 per 100,000 population; 17.5 for men and 13.5 for women. The global crude rate was 29.6; 31.4 for men and 27.8 for women. The global adjusted truncated rate was 23.9; 26.2 and 21.6 for men and women, respectively. The global truncated rate was 29.6; 31.4 for men and 27.7 for women. In the case of colon cancer, the global adjusted rate was 10.9 per 100,000 population; 12.1 for men and 9.8 for women. In the case of rectum cancer, 4.5; 5.3 for men and 3.7 for women. The incidence of colorectal cancer in the province of Guadalajara compared with Spain is medium, and compared with the rest of the world, median-low. The incidence trend is towards a progressive increase for the colon location of cancer among men of non-advanced age.

Role of interleukin-6 in acute pancreatitis. Comparison with C-reactive protein and phospholipase A.

Plasma values of immunoreactive interleukin-6, C-reactive protein and phospholipase A have been determined in serial samples from 24 patients with acute pancreatitis ('mild' pancreatitis nine, 'severe' pancreatitis 15). Median plasma concentrations of interleukin-6, C-reactive protein, and phospholipase A activity were significantly higher in patients with 'severe' illness (p < 0.001) than those with 'mild' illness. A particularly marked increase in interleukin-6 was found in two patients with necrotising pancreatitis and fatal outcome. Significant correlations between plasma concentrations of interleukin-6 and phospholipase A (p = 0.0218) and C-reactive protein and phospholipase A activity (p < 0.0001) were found in patients with 'severe' disease. These findings in a limited number of patients with acute pancreatitis are promising in that raised interleukin-6 correlated with clinical severity and with two other established markers, C-reactive protein, and phospholipase A activity.

Clinical usefulness of polymorphonuclear elastase in predicting the severity of acute pancreatitis: results of a multicentre study.

The usefulness and clinical applicability of quantitative plasma polymorphonuclear elastase determinations in the diagnosis of the severity of acute pancreatitis was analysed in a multicentre study and was compared with the usual prognostic systems of Ranson and Osborne et al. The study comprised 182 patients, 154 with a mild episode of acute pancreatitis and 28 with a severe episode, defined by the development of major complications or a fatal outcome. In the severe cases neutrophilic elastase reached significantly higher values than in mild cases (P less than 0.001) by the time the patient was admitted (2-12 h after the onset of the disease), reflecting considerable leucocyte activation. The sensitivity and specificity of this test are therefore greater than 90 per cent, with a positive severity predictive value of almost 80 per cent at the time of admission and 97 per cent after 24 h, and a negative predictive value of approximately 98 per cent. In addition to requiring 48 h for evaluation, the usual prognostic systems show a sensitivity of 77-85 per cent, a specificity of 70-77 per cent, a positive predictive value of 40-48 per cent, and a negative predictive value of 92-95 per cent, clearly lower than those obtained with leucocyte elastase. Polymorphonuclear elastase is therefore a very early and reliable marker in the diagnosis of the severity of acute pancreatitis, in addition to being easily adaptable to the routine of any hospital laboratory.

[An analysis of 14,000 patients admitted to an internal medicine service during 1982-1988]. / Análisis de 14.000 enfermos ingresados en un Servicio de Medicina Interna durante los años 1982-1988.

We analysed the discharge reports of patients admitted during 1982-1988 to an internal medicine department of a university hospital. There were 927 deaths among 13,913 patients (6.66%); the median age of the persons admitted was 59.50 years while the median age of the patients who died was 72.87 years. Both groups suffered from several afflictions; the most frequent among the hospital-admission group being: blood hypertension, pneumonia, diabetes mellitus, and the group who eventually died: pneumonia, cerebrovascular and neoplastic disease.